This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT: We propose to evaluate the effects of feeding premature infants with a human milk fortifier made entirely from human milk protein compared with using one made from cow s milk protein. Infants in Group 1 are those whose mothers will provide at least some breast milk. Infants in Group 2 are those who will not receive any mother's own milk. Comparisons will be based on the primary endpoint of days of total parenteral nutrition (TPN), as well as on parameters such as time to full enteral feeding (approximately 150-160 mL/kg/day), amount of IV fluid support, culture-proven sepsis, necrotizing enterocolitis (NEC), death, growth and short-term development, and incidence of feeding intolerance. HYPOTHESIS: The human milk-based fortifier will prove to have more positive effects on premature infants than the cow s milk-based fortifier will. The infants in Group 1 will have more positive results than infants in Group 2 as well. Positive effects will include decreased incidence of death, sepsis, or necrotizing enterocolitis, increased growth and development, shorter time on total parenteral nutrition, and decreased incidence of feeding intolerance. SPECIFIC AIMS: Rational: Ultimate demonstration of our hypothesis regarding the short term effects of human milk based fortifier made from human milk versus a fortifier made from cow s milk protein on premature infants. BACKGROUND AND SIGNIFICANCE: Breast milk is now considered the nutrition of choice for infants, including those in the NICU. Generally speaking, when breast milk is used in the NICU it is milk from the baby s own mother. In the case of very-low birth weight (VLBW) infants, this milk is generally supplemented with a human milk fortifier (HMF)in order to provide the extra nutrition that these babies need. Most of the data supporting the use of milk comes from studies done on babies receiving their own mother's milk. The case for the use of donor milk, in those situations where mother's milk is not available, is not as strong. Against this background of a preponderance of individually intriguing amounts of evidence appearing to point to a benefit to the use of human milk products including human-based fortification in the NICU in terms of decreasing the incidence of major complications, and equally uncertain studies purporting to find no advantage to the use of donor milk-based nutrition over bovine-based formula, the current set of studies will attempt to arrive at a definitive answer to the question, particularly with respect to the use of human versus bovine-based fortification.